chr4-99307788-T-C

Variant names:

• chr4-99307788-T-C
• rs17033
• NM_000668.6:c.*52A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000668.6(ADH1B):​c.*52A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,596,822 control chromosomes in the GnomAD database, including 9,301 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.097 (1046 hom., cov: 32)
  • Exomes 𝑓: 0.093 (8255 hom.)
• Consequence: ADH1B NM_000668.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 39 publications found

Genes affected

ADH1B (HGNC:250): (alcohol dehydrogenase 1B (class I), beta polypeptide) The protein encoded by this gene is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000668.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	NM_000668.6	MANE Select	c.*52A>G		3_prime_UTR	Exon 9 of 9	NP_000659.2
	ADH1B	NM_001286650.2		c.*52A>G		3_prime_UTR	Exon 10 of 10	NP_001273579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADH1B	ENST00000305046.13	TSL:1 MANE Select	c.*52A>G		3_prime_UTR	Exon 9 of 9	ENSP00000306606.8
	ADH1B	ENST00000625860.2	TSL:1	c.*52A>G		3_prime_UTR	Exon 9 of 9	ENSP00000486614.1
	ADH1B	ENST00000881106.1		c.*52A>G		3_prime_UTR	Exon 9 of 9	ENSP00000551165.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14779 AN: 152084 Hom.: 1039 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.0587

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0982

GnomAD4 exome AF: 0.0925 AC: 133643 AN: 1444618 Hom.: 8255 Cov.: 29 AF XY: 0.0902 AC XY: 64884 AN XY: 719728

African (AFR) AF: 0.0690 AC: 2270 AN: 32878

American (AMR) AF: 0.346 AC: 15389 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.0850 AC: 2213 AN: 26034

East Asian (EAS) AF: 0.0763 AC: 3021 AN: 39580

South Asian (SAS) AF: 0.0489 AC: 4199 AN: 85872

European-Finnish (FIN) AF: 0.126 AC: 6746 AN: 53374

Middle Eastern (MID) AF: 0.0789 AC: 451 AN: 5716

European-Non Finnish (NFE) AF: 0.0858 AC: 94137 AN: 1096792

Other (OTH) AF: 0.0872 AC: 5217 AN: 59856

GnomAD4 genome AF: 0.0973 AC: 14804 AN: 152204 Hom.: 1046 Cov.: 32 AF XY: 0.102 AC XY: 7593 AN XY: 74414

African (AFR) AF: 0.0692 AC: 2877 AN: 41556

American (AMR) AF: 0.239 AC: 3647 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.0884 AC: 458 AN: 5180

South Asian (SAS) AF: 0.0596 AC: 287 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1418 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5568 AN: 68002

Other (OTH) AF: 0.0995 AC: 210 AN: 2110

Alfa AF: 0.0892 Hom.: 1516

Bravo AF: 0.108

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17033; hg19: chr4-100228945;